C/EBPβ in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis. (July 2016)

• Record Type: Journal Article
• Authors: Rahman, Shaikh M.; Baquero, Karalee C.; Choudhury, Mahua; Janssen, Rachel C.; de la Houssaye, Becky A.; Sun, Ming; Miyazaki-Anzai, Shinobu; Wang, Shu; Moustaid-Moussa, Naima; Miyazaki, Makoto; Friedman, Jacob E.
• Is Part Of: Atherosclerosis. Volume 250(2016)
• Page Start: 172
• Page End: 179
• Publication Date: 2016-07
• Subjects: Atherosclerosis -- Bile acid -- Cytokine -- Hematopoietic stem cell -- Inflammation -- Macrophage foam cells -- Cholesterol efflux; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.03.040
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and Objective: Atherosclerosis is both a chronic inflammatory disease and a lipid metabolism disorder. C/EBPβ is well documented for its role in the development of hematopoietic cells and integration of lipid metabolism. However, C/EBPβ's role in atherosclerotic progression has not been examined. We assessed the impact of hematopoietic CEBPβ deletion in ApoE −/− mice on hyperlipidemia, inflammatory responses and lesion formation in the aorta. Methods and Results: ApoE −/− mice were reconstituted with bone marrow cells derived from either WT or C/EBPβ −/− mice and placed on low fat or high fat/high cholesterol diet for 11 weeks. Hematopoietic C/EBPβ deletion in ApoE −/− mice reduced blood and hepatic lipids and gene expression of hepatic stearoyl CoA desaturase 1 and fatty acid synthase while expression of ATP binding cassette transporter G1, cholesterol 7-alpha-hydroxylase, and liver X receptor alpha genes were significantly increased. ApoE −/− mice reconstituted with C/EBPβ −/− bone marrow cells also significantly reduced blood cytokine levels and reduced lesion area in aortic sinuses compared with ApoE −/− mice reconstituted with WT bone marrow cells. Silencing of C/EBPβ in RAW264.7 macrophage cells prevented oxLDL-mediated foam cell formation and inflammatory cytokine secretion in conditioned medium. Conclusion: C/EBPβ in hematopoietic cells is crucial to regulate diet-induced inflammation, hyperlipidemia and atherosclerosis development. Highlights: C/EBPβ regulates genes that control hyperlipidemia and inflammation. Hematopoietic C/EBPβ deletion in ApoE −/− mice prevents hyperlipidemia and atherosclerosis. C/EBPβ in hematopoietic-derived macrophages is partly responsible for the observed effects.